Stilbene useful for Positron Emission Tomography (PET) imaging of patient are known from WO2003/018070A1 and WO2006/066104A1. Stilbene are radiolabeled with 18F radioisotope whereas radiolabeling occurred in organic solution in presence of the stilbene precursor and [18F]. The stilbene precursor can be in a dry condition and optionally has an inert pharmaceutically acceptable carrier and/or auxiliary substances added thereto and a reducing agent and optionally a chelator. The fluoro-radiolabeled stilbene (PET tracer) solution may contain any additive such as pH controlling agents (e.g. acids, bases, buffers), stabilizers (e.g. ascorbic acid) or isotonizing agents (e.g. sodium chloride).
Ethanol, isopropanol, glycerol, and polyethylene glycol are well known as solubility-increasing excipients, WO2001/68142.
Usually, PET supply centers produce on demand a hot stock solution comprising the pharmaceutical that is injected to the patient along the working day. The hot stock solution must be stable and storable. Furthermore, a significant amount of newly synthesised PET tracer is lost during purification step(s) i.e. sterile filtration. Until now, there has been little published on formulations suitable for PET-pharmaceuticals.
Thus, there is a need for commercially acceptable suitable formulations comprising a PET agent, characterized in that the PET agent shows a low water solubility i.e. lipophilic PET agent, wherein the PET agent is an Amyloid beta ligand stilbene useful for PET imaging.
It has been surprisingly found that the claimed pharmaceutical formulation is chemically stable and can be stored at least for 8 hours and that this pharmaceutical formulation allows the sterile filtration using suitable filter material(s) without loss of activity.
It has been found that fluoro-radiolabeled stilbene are solubilized and stabilized by the formulation of present invention. Using this formulation, dilutions needed for adjustment of activity can be made in a wide range of dilution ratios, allowing the precise adjustment for any patient at any given time of the shelf life. It combines good local tolerability with easy applicability within the manufacturing process for the radiolabeled PET tracer.
Sterile filtration step is necessary for providing a sterile parenteral pharmaceutical formulation and the like for obtaining a suitable pharmaceutical solution for pharmaceutical use. Unfortunately, a critical loss of PET tracer is in many cases observed. Thus, there is a need for improving the purification steps leading to an increase of the radio-labelling yield.
It has been surprisingly found that the pharmaceutical formulation of the present invention is successfully used with a sterile filter reducing adsorption onto a sterile filter of the pharmaceutical.